MODULATION OF ANTIBODY KINETICS BY THE CELL-MEMBRANE ACTIVE AGENT TWEEN-80 IN-VIVO

The modulation of antibody uptake by the tumour has been crucial in ma ny radioantibody applications for delivering optimal dose for therapy. Our approach was to modulate the monoclonal antibody (MAb) uptake by using a surface detergent (Tween 80). Our Mab was raised against the t yrosine kinase receptor recombinant protein tie. Mice bearing Lewis lu ng carcinoma xenografts were studied after injecting I-125 labeled IgG (1) subclass monoclonal antibody 3c4c7g6 tie protein. The biodistribut ion was studied at 4, 24, 48, 72, 96 and 120 hours after intravenous i njection. Tween 80 was administered intratumourally, 0.04% of tumour v olume. Without Tween 80 the antibody half-lives in tumour were 90 hour s, in blood 39 bours, in liver 22 hours, and in kidney 52 hours, where as using intratumoural Tween 80 half-lives were in tumour 66 hours, in blood 26 hours, in liver 27.5 hours and in kidney 27.5 hours. Althoug h the Tween manipulation did not increase uptakes by organs, it did en hance clearance rate from the blood. This data indicates that antibody dose can be optimized by surface detergent, enhancing clearance witho ut any burden to critical organs. This might be crucial in adjusting d elivered radioimmunotherapy dose by changing the mean residence time o f an antibody.